Since there's no cure for phenylketonuria (PKU), you'll need to manage it throughout your life. But treatment advances, specialty foods, and new diagnostics in recent decades have improved the outlook for people with this rare disease that can slow development and cause other health problems.
Because of newborn screening, most cases are caught before there are severe effects on physical and intellectual development. And there's more on the horizon, as scientists strive to develop new medications and at-home diagnostic tools that could make life easier for PKU patients.
"Personalized medicine for PKU is really expanding," says Hope Northrup, MD, a professor and director of the Division of Medical Genetics in the Department of Pediatrics at McGovern Medical School at UTHealth Houston. "What is on the plate of options for patients has gotten dramatically better than when we only had diet."
What's Available Now for PKU Patients
Thanks to ongoing research, doctors have a much better understanding of PKU now than they did a few decades ago, Northrup said. Most people with PKU can stay healthy by making changes to their diet and maintaining low levels of phenylalanine (Phe). There are also medications that allow some PKU patients to add more protein to their diet. Here are the diet, medication, and therapy options currently available for PKU patients.
Diet
Protein contains the amino acid phenylalanine (Phe). With PKU, your body struggles to manage Phe, and it can build up in your blood. That's why you'll need to avoid high-protein foods, such as animal proteins, dairy products, and certain fruits and vegetables. But every PKU patient is different, and some can safely consume more Phe than others. Your doctor will help determine your daily Phe limit. It's important to keep track of how much protein and Phe you consume each day.
"Even 'regular' breads and pastas may have too much protein for some people with PKU," says Nikki Drilias, RD, CD, a registered metabolic dietitian at the University of Wisconsin-Madison's Waisman Center.
But along with foods that are naturally low in protein, you can eat special low-protein versions of many different foods. There are low-protein pastas, breads, and replacement eggs, for example. You may be able to eat nondairy versions of yogurt, cheese, and milk, such as coconut yogurt, rice milk, and vegan cheeses, which are lower in protein.
It's also important to supplement your diet with a special liquid mixture called formula. PKU formula has little or no Phe but is rich in nutrients and high in other amino acids that your body needs. There are different formulas for infants and toddlers, but older children and adults drink the same version. You can drink your formula with meals and snacks throughout the day, rather than all at once.
"Because we have to restrict natural protein, we have to give patients all of the other amino acids besides phenylalanine," Northrup says. "If we just restricted their protein and didn't give them the other amino acids, they would become protein deficient and be very, very sick."
When Northrup started her medical training 40 years ago, there were only a handful of formula options. Now, she estimates there are about 50 different formulas for PKU patients to choose from.
Medications
Most people with PKU don't make enough of an enzyme called phenylalanine hydroxylase (PAH). PAH converts Phe to tyrosine, an amino acid important for basic body functions, including building proteins. "But PAH doesn't work by itself," says Northrup. "It has an enzymatic cofactor, which is tetrahydrobiopterin" or BH4. The cofactor gives PAH a boost, helping it break down Phe.
Sapropterin (Kuvan). This medicine is a lab-made version of BH4. It comes in a tablet that you take by mouth and works for about 30% to 50% of patients, Northrup said. You still have to follow a PKU diet, but the medicine may allow you to eat "a little bit more protein." It became the first drug approved to treat PKU in 2007. In 2023, an observational study of 576 people with PAH deficiency in Europe, including children and adults, found that Kuvan is safe for long-term use.
Sepiapterin (Sephience). In July 2025, sepiapterin gained FDA approval for children and adults with PKU. Like BH4, sepiapterin helps PAH break down Phe, but it's "further up the pathway than BH4," Northrup says. That makes it a precursor of BH4, so it may be more effective than BH4 for some patients. It's an oral medication that you take once daily, but you'll still need to follow a protein-restricted diet.
Pegvaliase (Palynziq). This medicine works for some PKU patients, allowing them to eat significantly more protein. It was approved by the FDA in 2018 for use in adults and in 2026 for adolescents aged 12-17. Instead of focusing on PAH, pegvaliase boosts a different enzyme that breaks down phenylalanine. It's called phenylalanine ammonia lyase (PAL). PAL "converts the Phe to two compounds that your body can easily discard," Northrup says. You inject yourself with the medicine under your skin. It can have serious side effects, including anaphylaxis, joint pain, and rashes.
"Many patients are risk-averse," Northrup added. "But for my patients who have stuck it out and use this drug, many of them can eat pretty much whatever they want. The patients say to me that it changed their lives."
Supplements
Supplementing the diet with long-chain polyunsaturated fatty acids (LCPUFAs) and large neutral amino acids (LNAAs) helps the brain. LCPUFAs help with brain development, vision, and motor skills. LNAAs help keep Phe from flooding the blood-brain barrier. Your doctor will talk to you about whether you need to use supplements.
New Treatments on the Horizon
Another oral therapy for PKU called repinatrabit (JNT-517) is in phase 3 clinical trials. It blocks the reabsorption of Phe in the kidneys and is expected to work for all PKU patients, according to Wanda Meeteer, APNP, a nurse practitioner in the University of Wisconsin Department of Pediatrics' Division of Genetics and Metabolism.
NGGT002, a gene therapy developed by NGGT Inc., is in phase 1 and 2 clinical trials expected to finish in 2030. "Results thus far have been promising," Meeteer said. She added that five of the six patients who received a high dose of the therapy had normal Phe levels after three weeks. The first patient to be treated maintained normal Phe levels 40 weeks after receiving the therapy.
Diagnostic Tools Used Now
PKU is usually diagnosed soon after a baby is born. All newborns in U.S. hospitals have a blood test to screen for different conditions, including PKU. It's a quick test that collects a few drops of blood from a newborn's heel. If your baby's blood has high levels of Phe, they may need to have more tests done, such as genetic testing. Babies diagnosed with PKU should be put on a special diet by 2 weeks old, Northrup says.
Diagnostic Tools Being Studied
Throughout your life, you'll need to regularly submit blood samples to check your Phe levels. Some people take samples at home and mail them to a lab for testing, but other patients choose to or must have the test done in a lab. Companies are developing home Phe monitoring units that could make it easier for PKU patients to keep track of their levels.
"For many years, patients have begged to have some sort of home Phe monitoring device, like diabetics have" for insulin, Northrup says.
The Apatek HomeCheck System uses a smartphone-connected device to give PKU patients Phe readings in real time at home. The system received an FDA Breakthrough Device designation and is in clinical development.
A home urine test for Phe levels developed at Clemson University was studied in a one-year clinical trial in 2019.
The Ego Phe System, an at-home Phe level monitoring device, is currently being tested for accuracy and ease of use in an early-stage clinical trial.
What Advances Mean for PKU Patients
It can feel overwhelming to have to manage PKU throughout your life. New advances, like low-protein foods and medications, may give you some relief by letting you eat a wider variety of foods. Clinical trials of potential new PKU treatments and at-home Phe testing devices are also underway. While it could be months or years before the most cutting-edge advances become available to all PKU patients, Northrup feels certain that more progress is to come.
"It's a new day for PKU," she says. "There's a lot of hope that things are going to get better, and things have gotten better already for many people. I think it's very exciting."
